rs4887077

Variant names:

• chr15-78686022-C-T
• rs4887077
• ENST00000560511.5:n.228+21966G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000560511.5(CHRNB4):​n.228+21966G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.277 in 152,076 control chromosomes in the GnomAD database, including 7,360 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.28 (7360 hom., cov: 32)
• Consequence: CHRNB4 ENST00000560511.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.93
• Publications: 22 publications found

Genes affected

CHRNB4 (HGNC:1964): (cholinergic receptor nicotinic beta 4 subunit) This gene is found within a conserved gene cluster and encodes one of the beta subunits of the nicotinic acetylcholine receptor (nAChRs) superfamily which form ligand-gated ion channels with a central pore that forms a cation channel. Neuronal nAChRs are pentameric structures that can be either homomeric or heteromeric, with heteromeric structures containing both alpha and beta subunits. Each subunit contains an extracellular amino terminus and four transmembrane domains. Nicotine is one of the agonists that binds to the receptor. Variants in this gene have been associated with nicotine dependence and lung cancer. Alternative splicing results in multiple transcript variants encoding different isoforms. [provided by RefSeq, Sep 2017]

CHRNB4 Gene-Disease associations (from GenCC):

• lung cancer

  Inheritance: AD Classification: LIMITED Submitted by: Ambry Genetics

ENSG00000290426 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.402 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CHRNB4	ENST00000560511.5	n.228+21966G>A		intron_variant	Intron 2 of 6	3
ENSG00000290426	ENST00000569846.2	n.367-6660C>T		intron_variant	Intron 2 of 5	4
ENSG00000290426	ENST00000846725.1	n.401-6660C>T		intron_variant	Intron 1 of 5

Frequencies

GnomAD3 genomes AF: 0.278 AC: 42191 AN: 151958 Hom.: 7356 Cov.: 32

Gnomad AFR AF: 0.0916

Gnomad AMI AF: 0.361

Gnomad AMR AF: 0.257

Gnomad ASJ AF: 0.346

Gnomad EAS AF: 0.0250

Gnomad SAS AF: 0.216

Gnomad FIN AF: 0.324

Gnomad MID AF: 0.380

Gnomad NFE AF: 0.406

Gnomad OTH AF: 0.301

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.277 AC: 42201 AN: 152076 Hom.: 7360 Cov.: 32 AF XY: 0.272 AC XY: 20208 AN XY: 74316

African (AFR) AF: 0.0916 AC: 3803 AN: 41522

American (AMR) AF: 0.257 AC: 3920 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.346 AC: 1202 AN: 3470

East Asian (EAS) AF: 0.0255 AC: 132 AN: 5180

South Asian (SAS) AF: 0.218 AC: 1047 AN: 4798

European-Finnish (FIN) AF: 0.324 AC: 3424 AN: 10554

Middle Eastern (MID) AF: 0.374 AC: 110 AN: 294

European-Non Finnish (NFE) AF: 0.406 AC: 27605 AN: 67960

Other (OTH) AF: 0.298 AC: 630 AN: 2114

Alfa AF: 0.305 Hom.: 2386

Bravo AF: 0.265

Asia WGS AF: 0.115 AC: 402 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.066
DANN	Benign	0.66
PhyloP100		-1.9

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs4887077; hg19: chr15-78978364;